| Optimizing Screening and Risk Assessment for Suicide in the U. S. Military |
Sep 2011 |
19 pages |
| Authors:
Thomas Joiner; FLORIDA STATE UNIV TALLAHASSEE
|
 | All IRB approvals are complete. This study has now been up and running full swing since 10/4/11. We have collected approximately 225 Participants thus far. Suicide rates have been increasing in military personnel in the last several years (Lorge, 2008), and it is a vital goal that suicide screening and risk assessment techniques for members of the military be improved. The proposed project is an effort to accomplish this goal, ... |
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| Dual-Modality Prostate Imaging with PET and Transrectal Ultrasound |
Sep 2011 |
53 pages |
| Authors:
Jennifer Huber; CALIFORNIA UNIV BERKELEY
|
| We developed the hardware and software tools needed for dual Positron Emission Tomography-Transrectal Ultrasound (PET-TRUS) imaging of the prostate. We modified the TRUS equipment to work when mounted on a scanner table in conjunction with both the LBNL prostate-optimized and Siemens EXACT HR PET scanners. We developed software to: determine the location of point sources and calculate the corresponding location of the TRUS probe tip (both in PET coordinates), reconstruct ... |
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| Regulation of Breast Cancer Cell Motility by Golgi-Mediated Signaling |
Sep 2011 |
10 pages |
| Authors:
Ian P Whitehead; UNIVERSITY OF MEDICINE AND DENTISTRY OF NEW JERSEY NEWARK
|
| We have previously determined that the Rho-specific guanine nucleotide exchange factor, Dbs, regulates both normal and tumor cell motility. Since full-length Dbs localizes to the Golgi, we have determined whether Golgi-mediated signaling activities are required for breast cancer cell movement. Thus, stable MDA-MB-231 cell lines were established in which the activity of Golgi-localized Dbs was suppressed by a novel Sec14 domain-mediated genetic inhibitor. The level of endogenous activated Cdc42 was ... |
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| Flying Blind: Aeromedical Certification and Undiagnosed Age-Related Macular Degeneration |
Sep 2011 |
14 pages |
| Authors:
Van B Nakagawara; Ronald W Montgomery; FEDERAL AVIATION ADMINISTRATION OKLAHOMA CITY OK CIVIL AEROSPACE MEDICAL INST
|
| The love of flying seldom diminishes throughout a pilot's career. It is often the primary motivation for investing the time and expense necessary to attain and maintain a valid pilot license and medical certificate. However, a pilot's ability to meet the physical requirements for aeromedical certification may become compromised by advancing age or impairments. Individuals with physical limitations or the elderly in a number of states must pass a vision ... |
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| Deregulation of miRNAs Contributes to Development and Progression of Prostate Cancer |
Sep 2011 |
29 pages |
| Authors:
Ralph W deVere White; CALIFORNIA UNIV DAVIS
|
| This DOD grant aims to identify biomolecules that are crucial in the pathogenesis of prostate cancer. In the first year we found that miR-125b directly targets p53, Puma and Bak1. In the 2nd year, we focused on Aim 2 and have obtained exciting results: 1) miR-125b promotes prostatic tumor growth and also induces castrate-resistant growth in a mouse model; 2) miR-125-mediated suppression of apoptosis signaling contributes to the growth of ... |
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| The Role of microRNA miR-101 in Prostate Cancer Progression |
Sep 2011 |
50 pages |
| Authors:
Qi Cao; MICHIGAN UNIV ANN ARBOR
|
| Polycomb group (PcG) proteins are chromatin-modifying complexes that regulate epigenetic silencing and play an important role in determining cell fate. PcG proteins form two major complexes, Polycomb Repressive Complex 1 (PRC1) and Polycomb Repressive Complex 2 (PRC2). PRC2 methylates histone H3 on lysine27 (H3K27) creating a chromatin mark which stimulates PRC1 to enact gene silencing at target genes. Employing in vitro and in vivo cancer models, combined with human tumor ... |
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| Control of Metastatic Colonization in Prostate Cancer: The Functional Mechanism of Metastasis Suppression by JNKK1/MKK4 |
Sep 2011 |
21 pages |
| Authors:
Russell Szmulewitz; CHICAGO UNIV IL
|
| The purpose of the award was to provide Dr. Szmulewitz with training in basic and translational prostate cancer (PC) research. The scientific focus is PC metastasis modeling and modulation of metastatic colonization (the specific outgrowth of microscopic disseminated cancer cells to overt macroscopic metastases) through the prostate cancer metastasis suppressor JNKK1/MKK4. In addition the scope of the award also includes key training opportunities. Over the second year of this award ... |
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| Breast Cancer: Catch It with Ultrasound |
Sep 2011 |
5 pages |
| Authors:
Michael Williamson; Lianjie Huang; Francesco Simonetti; Kenneth Hanson; Martin Montoya-Zavala; Silva Krause; Heather Tobin; Robert Rosenberg; Philip Heintz; NEW MEXICO UNIV ALBUQUERQUE
|
| Our multi-team group (Los Alamos National Laboratories (LANL) and Children s Hospital Boston and Harvard Medical School) aims to develop the next-generation ultrasound (US) technology that combines the biomechanical aspects of cancer progression with advanced 3D image reconstruction. The UNM team will initially create imaging case studies that compare findings of common pathology and normal anatomy of the conventional modalities and US tomography. UNM will use this information for subsequent ... |
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| Convection-Enhanced Delivery (CED) in an Animal Model of Malignant Peripheral Nerve Sheath Tumors and Plexiform Neurofibromas |
Sep 2011 |
8 pages |
| Authors:
Kaleb Yohay; CORNELL UNIV MEDICAL COLL (WEILL) NEW YORK
|
| Due to delays in obtaining regulatory approval from both our own IACUC and the DOD, we were unable to begin our study until very recently. Despite the delays, we have made progress in establishing the cell lines necessary for the study to proceed, characterization of the cell lines, and further developing and establishing surgical methods for sciatic implantation and convection enhanced delivery within the tumors. Despite the delays, we are ... |
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| The Role of miRNAs in the Progression of Prostate Cancer from Androgen-Dependent to Androgen-Independent Stages |
Sep 2011 |
44 pages |
| Authors:
Dandan Sun; VIRGINIA UNIV CHARLOTTESVILLE
|
| We used two genomic strategies for microRNA profiling, next generation sequencing and Locked Nucleic Acid miRNA microarrays, and verified the concordant changes by quantitative RT-PCR. miR-125b and members of miR-99 family (miR-99a, -99b, -100) were down-regulated in all three assays in the more advanced prostate cancer cell line C4-2 relative to the parental LNCaP cells. Similar decrease was seen in the transformed prostate cancer cell line WPE1-NB26 compared to its ... |
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| Sealing Penetrating Eye Injuries Using Photoactivated Bonding |
Sep 2011 |
8 pages |
| Authors:
Anthony Johnson; HENRY M JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE ROCKVILLE MD
|
| To develop a light-activated technology (called PTB) with the potential to decrease vision loss and ocular complications in warfighters sustaining penetrating eye injuries. Scope: In year 2, the scope was to establish the treatment for direct photo-sealing of corneal lacerations, to identify the best treatment for sealing eyelid skin lacerations, and to optimize and build a prototype light delivery system that is safe for the retina. Major findings: Demonstrated that ... |
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| The Role of Tumor Associated Macrophage in Recurrent Growth of Tumor Stem Cell |
Sep 2011 |
7 pages |
| Authors:
Aya Kobayashi; SOUTHERN ILLINOIS UNIV SCHOOL OF MEDICINE SPRINGFIELD
|
| The pro-inflammatory microenvironment in the tumor is established by first recruiting various leukocytes including tumor-associated macrophage (TAM) which is believed to promote tumor growth and angiogenesis, suppress adaptive immunity, and hence remodel tumor microenvironment. According to the recent cancer stem cell (CSC) theory, recurrent tumor must arise from a dormant tumor stem cell whose re-growth is triggered by shifting of microenvironment. This project aims at clarifying the roles of TAM ... |
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| Identification of Druggable Proteins Regulating Receptor Recycling in Breast Cancer Cells |
Sep 2011 |
5 pages |
| Authors:
Guangwei Du; Ping Wu; Yoshiya Yonekubo; Melissa Wilmarth; TEXAS UNIV HEALTH SCIENCE CENTER AT HOUSTON
|
| Increased receptor recycling leads to elevated receptors on the plasma membrane, thereby augments signaling cascades important in cancer progression and drives tumor aggressiveness. Inhibition of the altered recycling pathway in breast cancer cells would thus dampen oncogenic signaling and increase the efficacy of therapy. We propose to monitor EGFR trafficking using a newly developed AP-tag (or Avitag) system. We have generated functional constructs for the label of EGFR using AP-tag ... |
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| Tracking Origins of Prostate Cancer - An Innovative in vivo Modeling |
Sep 2011 |
9 pages |
| Authors:
Kethandapatti C Balaji; Xiaolan Fang; Kennyth Gyabaah; Sandy Sink; WAKE FOREST UNIV WINSTON-SALEM NC
|
| Heterogeneity, variable and often unpredictable clinical course are fundamental challenges in management of patients with prostate cancer. To make rapid advances in understanding of disease mechanism that can be translated to clinical care in short order, there is an immediate need for innovative in vivo disease models that accurately recapitulate human disease at cellular level. We propose to develop an innovative and hitherto not attempted in vivo prostate cancer model ... |
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| DCIS-Specific MicroRNA in Cancer Stem Cell |
Sep 2011 |
9 pages |
| Authors:
Kounosuke Watabe; SOUTHERN ILLINOIS UNIV SPRINGFIELD
|
| More than 20% of breast cancer patients detected by mammography are DCIS and this number keeps on increasing (1). Although DCIS is a non-invasive benign tumor, it is considered a precursor of malignant cancer. Therefore, understanding the molecular changes from normal cell to DCIS is of paramount importance and it is under intensive study. However, the exact mechanism of normal-DCIS transition is still not well understood. The purpose of this ... |
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| Identification of Metastatic Tumor Stem Cell |
Sep 2011 |
9 pages |
| Authors:
Kounosuke Watabe; SOUTHERN ILLINOIS UNIV SPRINGFIELD
|
| More than 90% of deaths caused by breast cancer are attributed to metastatic disease. However, the exact molecular mechanism of tumor metastasis is still poorly understood. It has been well recognized that only a fraction of cells in the primary tumor eventually metastasizes to the distant organs; however, the origin and nature of these cells are still unclear. The purpose of this project is to test our novel hypothesis that ... |
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| Imaging Molecular Signatures of Breast Cancer With X-ray Activated Nano-Phosphors |
Sep 2011 |
32 pages |
| Authors:
Colin M Carpenter; LELAND STANFORD JUNIOR UNIV CA
|
| The first year of this research program developed the foundation for a new medical imaging modality, now called Radioluminescence Tomography (RLT), which utilizes biologically compatible phosphor nanoparticles to produce images of molecular breast cancer contrasts. The development of this modality is significant to the early detection of breast cancer, and to provide feedback to guide Radiation Therapy, for such breast cancer treatments as Intraoperative Radiation Therapy. The work in Year ... |
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| Signature and Mechanism of the Epitehlial-to-Mesenchymal Transition. Addendum |
Sep 2011 |
13 pages |
| Authors:
Kong J Kah; MASSACHUSETTS INST OF TECH CAMBRIDGE
|
| The Epithelial-to-Mesenchymal Transition (EMT) is a conserved developmental process that is thought to be reactivated during the metastasis of epithelial cancers such as breast cancer. This study seeks to identify genes commonly regulated in the EMT, and identify key regulators of the process. An EMT core gene signature of approximately 1000 genes was generated, from which the transcription factor Zeb1 emerged as a potent key regulator of the EMT. Zeb1 ... |
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| Engineered PlyCB as Novel Implant Coating for Osseointegration |
Sep 2011 |
11 pages |
| Authors:
Daniel C Nelson; MARYLAND UNIV COLLEGE PARK
|
| During the performance period, we successfully constructed five RGD or cyclic-RGD containing mutants to PlyCB. Four of them were to the N-terminus and one was to the external loop between helicies 1 and 2 of PlyCB. All five mutants were expressed, purified, and analyzed to confirm retention of wild-type properties. These tests included analytical gel filtration/dynamic light scattering (to confirm self assembly of PlyCB into an octameric ring) and thermal ... |
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| Role of Cathepsin C During Breast Cancer Metastasis |
Sep 2011 |
65 pages |
| Authors:
Brian Ruffell; CALIFORNIA UNIV SAN FRANCISCO
|
| The presence of some innate immune cell types in developing neoplasms provides a significant pro-tumor advantage. Myeloidlineage immune cells, such as tumor-associated macrophages (TAMs) and immature myeloid-derived cells/monocytes, promote tumor development by exerting pro-tumor activities including activating angiogenic programs, suppressing anti-tumor immunity, and enhancing migratory and metastatic properties of malignant cells. We have now established in both murine models and human patients that exposure to neoadjuvant chemotherapy induces the recruitment ... |
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| Noninvasive Thermal Ablation of Osteomyelitis-Causing Bacteria Using Functionalized Nanoparticles |
Sep 2011 |
12 pages |
| Authors:
Daniel C Nelson; MARYLAND UNIV COLLEGE PARK
|
| During the performance period, we successfully constructed an N-terminal serine to cysteine mutant of PlyCB. This mutant was expressed, purified, reacted with gold nanoparticles and the resulting PlyCB/gold nanoparticle complex was then purified. A fraction of the complex was further conjugated to a fluorescent dye and specific binding of the complex to streptococcal cells, but not non-target cells, was observed by both bright field and fluorescent microscopy. Next, the nanoparticles ... |
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| Estrogen and the Dietary Phytoestrogen Resveratrol as Regulators of the Rho GTPase Rac in Breast Cancer Metastasis |
Sep 2011 |
87 pages |
| Authors:
Suranganie Dharmawardhane; PUERTO RICO UNIV SAN JUAN
|
| The hypothesis that estrogen and low concentrations of resveratrol promote breast cancer invasion and metastasis while high concentrations of resveratrol prevent breast cancer metastasis via regulation of Rac was tested. Results from Specific Aim 1 demonstrated that dependent on estrogen receptor (ER) status, E2 and resveratrol have differential effects on Rac activity, cell migration/invasion, and cell growth. Specific Aim 2, we tested the effect of resveratrol on mammary tumor growth ... |
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| T-Cell Immunotherapies for Treating Breast Cancer |
Sep 2011 |
19 pages |
| Authors:
Laurence Cooper; M D ANDERSON CANCER CENTER HOUSTON TX
|
| Breast cancer is the most commonly diagnosed cancer among U.S. women (approximately 28% or more than 1 in 4) with approximately 1 in 8 women expected to develop this malignancy over the course of her lifetime. In 2010, there are an estimated 207,000 newly diagnosed cases of invasive breast cancer resulting in about 39,800 deaths in the United States, a mortality rate higher than all other malignancies, except lung cancer. ... |
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| Intraoperative Molecular Imaging for Rapid Assessment of Tumor Margins |
Sep 2011 |
12 pages |
| Authors:
Scott Davis; DARTMOUTH COLL HANOVER NH
|
| The objective of this research is to develop methods for rapid detection of tumor margins during breast cancer surgery using targeted fluorescence-labeled tracers and thus reduce the high rate of repeat surgery. We have developed and characterized a spectrometer-based fluorescence probe system to quantify fluorescence signals in excised tissue. Spectral processing techniques allowed the removal of contaminating tissue auto-fluorescence and provided highly linear responses to reporter concentration. Additionally, a new ... |
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| TPD52: A Novel Vaccine Target for Prostate Cancer |
Sep 2011 |
20 pages |
| Authors:
Robert Bright; TEXAS TECH UNIV HEALTH SCIENCES CENTER LUBBOCK
|
| Tumor protein D52 (D52) is a novel self-onco-antigen involved in cellular transformation, proliferation and metastasis that is over-expressed in prostate cancer cells. The overall goal of this Award is to test the efficacy of D52-based vaccines in the TRAMP murine model of prostate cancer, and to characterize vaccine induced mechanisms of tumor immunity. Due to unforeseen circumstances during this funding period primarily involving the animal vendor and maternity leave for ... |
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| The Role of Polycomb Group Gene Bmi-1 in the Development of Prostate Cancer |
Sep 2011 |
47 pages |
| Authors:
Mohammad S Bhat; TWIN STAR MEDICAL MINNEAPOLIS MN
|
| We proposed to investigate the role of Bmi-1 (a member of polycomb gene family) in human prostate cancer (CaP) development. Here, we present the work accomplished during the last 5 months (after submitting the 1st annual report ) of the project. In 1st annual report we showed that Bmi-1 protein levels are highly elevated in human CaP patients and we investigated the mechanistic basis of the role of Bmi-1 in ... |
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| Genes Associated with Food Allergy and Eosinophilic Esophagitis |
Sep 2011 |
5 pages |
| Authors:
David Broide; CALIFORNIA UNIV SAN DIEGO LA JOLLA
|
| The ingestion of food antigens plays an essential role in the development of eosinophilic esophagitis (EE) as total removal of dietary antigens by using an amino acid based oral formula improves clinical symptoms and esophageal histology in 98% of patients with EE within a month. EE is thought to be mediated by both IgE and non-IgE mediated food allergy. In this study we are particularly interested in identifying genes in ... |
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| Systems-Level Analysis of EGFR Inhibition-DNA Damage Combination Treatment in Breast Cancer |
Sep 2011 |
40 pages |
| Authors:
Michael J Lee; MASSACHUSETTS INST OF TECH CAMBRIDGE
|
| Triple--negative breast cancer (TNBC) is a heterogeneous mix of cancers defined only by their lack of estrogen receptor expression, lack of progesterone receptor expression, and lack of amplification of the oncogene HER2. This lack of molecular etiology has limited our ability to rationally design therapies for TNBC, resulting in shorter relapse-free survival and a worse overall prognosis than other breast cancer patients. Here, we systematically screened various drug combinations, looking ... |
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| Development of a PTSD Population Registry |
Sep 2011 |
8 pages |
| Authors:
Raymond C Rosen; NEW ENGLAND RESEARCH INST INC WATERTOWN MA
|
| The purpose of this project is to develop the first longitudinal registry of combat-exposed men and women with posttraumatic stress disorder (PTSD). This registry will provide essential data on the natural history and outcomes associated with PTSD in military service men and women who have utilized the Department of Veterans Affairs (VA) health care system. An additional goal of this project is to evaluate risk factors for PTSD among combat-exposed ... |
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| Development of a PTSD Population Registry |
Sep 2011 |
8 pages |
| Authors:
Terence Keane; BOSTON VA RESEARCH INST MA
|
| The purpose of this project is to develop the first longitudinal registry of combat-exposed men and women with posttraumatic stress disorder (PTSD). This registry will provide essential data on the natural history and outcomes associated with PTSD in military service men and women who have utilized the Department of Veterans Affairs (VA) health care system. An additional goal of this project is to evaluate risk factors for PTSD among combat-exposed ... |
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| Inhibition of Interleukin-4, a Survival Factor for Breast Cancer Cells, as an Antimetastatic Approach |
Sep 2011 |
14 pages |
| Authors:
Barbara Fingleton; VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
|
| Our goal was to determine the effects on metastasis of deleting or inhibiting the receptor for interleukin-4 from breast tumor cells. We proposed three aims: [1] Establish and characterize mammary tumor lines with the receptor for IL4 knocked down. [2] Determine the in vivo growth characteristics of IL4R-knockdown cells using spontaneous and experimental metastasis models; [3] Determine the therapeutic efficacy of IL4 neutralizing antibody in combination with chemotherapy in a ... |
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| Fibronectin Matrix Remodeling in the Regulation of the Inflammatory Response within the Lung: An Early Step in Lung Cancer Progression |
Sep 2011 |
15 pages |
| Authors:
Paula J McKeown-Longo; Anthony Ambesi; Carol Horzempa; Aparna Prasad; ALBANY MEDICAL COLL NY
|
| Changes in tissue mechanics as well as increased tissue inflammation have been identified as contributory factors to the development of malignancies. These pathologies are characterized by extensive remodeling of extracellular matrix and increased tissue rigidity. Recent studies have shown that increased tissue rigidity is associated with the unfolding of the Type III domains of extracellular matrix fibronectin. During the previous funding year, we have addressed the hypothesis that changes in ... |
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| Chemotheraphy, Neurotoxicity, and Cognitive Decline: Developing a Mouse Model and Potential Interventions |
Sep 2011 |
11 pages |
| Authors:
Thane Fremouw; MAINE UNIV AT ORONO
|
| Adjuvant chemotherapy often causes cognitive decline in breast cancer survivors. Although the cognitive deficits are often temporary, it appears that for at least a subset of survivors, the deficits last for years and can have a deleterious impact on survivor quality of life. Recent evidence shows that chemotherapy agents can have long-lasting neurotoxic effects: increase in cell death and decrease in cell division/proliferation in the SVG, the DG, and the ... |
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| A Novel Multi-voxel Based Quantitation of Metabolites and Lipids Non-invasively Combined with Diffusion Weighted Imaging in Breast Cancer |
Sep 2011 |
13 pages |
| Authors:
Michael A Thomas; CALIFORNIA UNIV LOS ANGELES
|
| Purpose: (1) To extend the single-voxel based 2D MRS version of L-COSY to multi-voxel based analogue on a 3T MRI/MRS scanner using the echo-planar imaging (EPI) based spatial encoding for determining metabolic distributions over many voxels; (2) To implement a Matlab-based post-processing algorithm in order to process the 2D COSY data recorded in breast cancer; (3) To record DWI and to calculate ADC maps in breast cancer patients and healthy ... |
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| Understanding Collagen Organization in Breast Tumors to Predict and Prevent Metastasis |
Sep 2011 |
48 pages |
| Authors:
Edward Brown; ROCHESTER UNIV NY
|
| The ordering of collagen fibers within a tumor has significant influence on tumor metastasis: in murine breast tumor models, tumor cells move towards blood vessels along fibers that are visible via second harmonic generation (SHG), and SHG is exquisitely sensitive to molecular ordering. Tumor cells that are moving along SHG-producing (i.e. ordered) collagen fibers move significantly faster than those cells that are moving independently of SHG-producing fibers, and the extent ... |
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| A Randomized Effectiveness Trial of a Systems-Level Approach to Stepped Care for War-Related PTSD |
Sep 2011 |
10 pages |
| Authors:
Lisa Jaycox; RAND CORP SANTA MONICA CA
|
| The purpose of the STEPS UP (STepped Enhancement of PTSD Services Using Primary Care) trial is to compare centralized telephonic care management with preference-based stepped PTSD and depression care to optimized usual care. We hypothesize that the STEPS UP intervention will lead to improvements in (1) PTSD and depression symptom severity (primary hypothesis); (2) anxiety and somatic symptom severity, alcohol use, mental health functioning, work functioning; (3) costs and cost-effectiveness. ... |
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| Early Diagnosis, Treatment and Care of Cancer Patients |
Sep 2011 |
18 pages |
| Authors:
Richard Fisher; Craig T Jordon; ROCHESTER UNIV NY SCHOOL OF MEDICINE AND DENTISTRY
|
| This grant program encompasses two complimentary projects. The hypothesis that leukemia can be treated effectively by inhibition of putative cancer stem cells will be tested in project #1. This will be done by application of inhibitors of stem cells as a novel approach for eradication of leukemia tumor cells. Parthenolide (PTL)-based drugs and related drugs that inhibit nuclear factor kappa B (NF- B) will be used. The effects of these ... |
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| Medial Prefrontal Cortex and HPA Axis Roles in Generation of PTSD-Like Symptoms in SPS Model |
Sep 2011 |
28 pages |
| Authors:
Israel Liberzon; Dayan Knox; Sophie George; MICHIGAN UNIV ANN ARBOR
|
| The research we have conducted over the third year of this research program is contained in this report. We have made substantial progress towards completing all of the proposed research in this program within proposed time frame i.e. final report on 9/29/12. During the last year, we have demonstrated that (1) decreases in neural activity in the BLA and hippocampus are critical for SPS-enhanced fear renewal (specific aims #1a and ... |
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| Hormonal Resistance And Metastasis ER-Coregulartor-Src Signaling Targeted Therapy |
Sep 2011 |
56 pages |
| Authors:
Ratna Vadlamudi; TEXAS UNIV AT SAN ANTONIO HEALTH SCIENCE CENTER
|
| The estrogen receptor (ER) is implicated in the progression of breast cancer. Despite positive effects of hormonal therapy, initial or acquired resistance to endocrine therapies frequently occurs. To establish the significance of ER-Src axis in PELP1 and HER2 mediated therapy resistance, we have generated model cells that stably express Src-shRNA under conditions of PELP1, HER2 deregulation. Depletion of Src using shRNA substantially reduced E2 mediated activation of Src and MAPK ... |
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| Development of Mouse Models of Ovarian Cancer for Studying Tumor Biology and Testing Novel Molecularly Targeted Therapeutic Strategies |
Sep 2011 |
27 pages |
| Authors:
Alnawaz Rehemtulla; MICHIGAN UNIV ANN ARBOR
|
| The objective of this project was to create genetically engineered mouse (GEM) models that in addition to developing ovarian carcinomas similar to human endometrioid carcinomas, also express a reporter for Caspase-3 activity, a hallmark of cells undergoing apoptosis. During the three year funding period, we generated stable lines of transgenic mice carrying a Cre-inducible luciferase reporter or apoptosis reporter and verified function of the reporter transgenes in vivo. Using Apcflox/flox;Ptenflox/flox;ROSA26LSL-Luc/+ ... |
|
| Development Of A Vaccine Targeting Triple-Negative Breast Cancer |
Sep 2011 |
9 pages |
| Authors:
Denise Cecil; SEATTLE UNIV WA
|
| The insulin-like growth factor (IGF) pathway plays an important role in breast cancer growth and metastasis. The IGF-I receptor (IGF-IR) is over-expressed in almost 50% of triple negative breast cancers (TNBC). Thus, therapeutically targeting tumor cells which have upregulated IGF-IR may be a promising approach to treat TNBC. IGF-IR is immunogenic in breast cancer and is a potential target for active immunization. We sought to develop a vaccine that will ... |
|
| New Advanced Technologies In Stem Cell Therapy |
Sep 2011 |
52 pages |
| Authors:
Johnny Huard; PITTSBURGH UNIV PA
|
| We have isolated and characterized a population of skeletal muscle-derived stem cells (MDSCs) that display a greatly improved skeletal and cardiac muscle transplantation capacity when compared to skeletal muscle myoblasts. The MDSCs ability to withstand oxidative and inflammatory stresses appears to be the single most important factor for their improved transplantation capacity. Although the true origin of MDSCs remains unclear, their high degree of similarity with blood vessel-derived stem cells ... |
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| Neural Mechanisms Linking Mild Traumatic Brain Injury and Anxiety States in an Animal Model |
Sep 2011 |
45 pages |
| Authors:
Gina Forster; Michael Watt; Pat Manzerra; SOUTH DAKOTA UNIV VERMILLION
|
| Previous correlational studies suggest that mild traumatic brain injury (TBI) is associated with an increase in the prevalence of anxiety disorders, including posttraumatic stress disorder (PTSD). By using a relevant animal model, this research demonstrates that mild TBI can result in increased fear learning and anxiety states that mimic the symptoms of generalized anxiety disorder and PTSD. Furthermore, this research suggests that heightened fear and anxiety states following mild TBI ... |
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| Breast Cancer-Targeted Nuclear Drug Delivery Overcoming Drug Resistance for Breast Cancer Chemotherapy |
Sep 2011 |
16 pages |
| Authors:
Youqing Shen; Maciej Radosz; William J Murdoch; WYOMING UNIV LARAMIE
|
| Cell membrane-associated and intracellular drug resistance mechanisms are the major cause of breast cancer treatment failure. The aim of this proposal is to develop nuclear localizing nanoparticles to delivery DNA-toxins breast cancer cell nuclei to effectively overcoming the drug resistance. We finished the task 1 - To synthesize and optimize folic-acid- or LHRHfunctionalized charge reversal nanoparticles. The cationic polymer PEI and its block copolymer with degradable PCL were synthesized. The ... |
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| Disequilibrium After Traumatic Brain Injury: Vestibular Mechanisms |
Sep 2011 |
26 pages |
| Authors:
Mark Walker; CASE WESTERN RESERVE UNIV CLEVELAND OH
|
| The purpose of this study is to investigate mechanisms of disequilibrium and imbalance in veterans of Operation Enduring Freedom / Operation Iraqi Freedom who have experienced traumatic brain injury (TBI). The mechanism of chronic dizziness and imbalance after TBI is not known. The hypothesis for this study is that TBI leads to an impairment in the vestibular reflexes that compensate for linear movements of the head and body during standing ... |
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| Identification of New Substrates for Breast Tumor-Specific LMW Cyclin E/CDk2 Kinase |
Sep 2011 |
12 pages |
| Authors:
Said Akli; M D ANDERSON CANCER CENTER HOUSTON TX
|
| Cyclin E overexpression occurs in 25% of breast cancer tumors and is linked to poor prognosis. In tumor cells full length cyclin E (FL-E) is processed by an elastase-like protease into low-molecular weight isoforms (LMW-E) that are biochemically hyperactive. We recently demonstrated in a transgenic mouse model that CDK2 is required for LMW-E-induced breast cancer. The hypothesis is that the biological and biochemical differences between FL-E and LMW-E may be ... |
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| Characterizing and Targeting Androgen Receptor Pathway-Independent Prostate Cancer |
Sep 2011 |
13 pages |
| Authors:
Phillip Febbo; CALIFORNIA UNIV SAN FRANCISCO
|
| In this proposal, we aim to test the hypothesis that complete AR pathway inhibition selects for subpopulations of tumor cells that are completely independent of AR signaling and further, that these resistant cells will have activated---and be dependent upon---a limited set of specific survival and growth regulatory pathways (stemming from genomic alterations in specific oncogene networks) that can be identified and targeted. We propose three aims to test our hypotheses. ... |
|
| Platelet Glycoprotein lb-1X and Malignancy |
Sep 2011 |
54 pages |
| Authors:
Jerry Ware; ARKANSAS UNIV AT LITTLE ROCK MEDICAL CENTER
|
| This report describes studies that document the use of mouse models of platelet dysfunction in the progression of cancer to metastatic disease. The work used genetically modified mouse strains with dysfunctional platelet membrane receptors. The studies examined the relevance of platelet receptors in models of spontaneous metastasis and models of experimental metastasis. A transgenic C57BL/6J mouse colony expressing MMTV-PyV middle antigen in mammary epithelium and dysfunctional platelets was developed. Mammary ... |
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| Targeting Thromboxane A2 Receptor for Anti-Metastasis Therapy of Breast Cancer |
Sep 2011 |
39 pages |
| Authors:
Daotai Nie; SOUTHERN ILLINOIS UNIV SCHOOL OF MEDICINE SPRINGFIELD
|
| Dissemination and metastasis of tumor cells are major causes of morbidity and mortality in breast cancer patients. Therefore it is of vital importance to identify druggable targets to inhibit breast tumor invasion and metastasis. A critical component in the invasive growth, dissemination, and metastasis of cancer is acquisition of motility by tumor cells. Our preliminary studies suggest a novel role for the thromboxane A2 receptor (TP) in controlling breast tumor ... |
|
| Advances In Breast Cancer Therapy |
Sep 2011 |
10 pages |
| Authors:
Hong Ma; PRECISION THERAPEUTICS INC PITTSBURGH PA
|
| A total of two hundred eight (208) specimens have been submitted to Precision for this study. One hundred twenty-two (122) subjects have been enrolled in this study to date. Out of those patients, thirty-five (35) were discontinued. Thirty-two (32) subjects were discontinued for not having a chemoresponse assay result, two (2) subjects were discontinued for being lost to follow-up, and one (1) subject was discontinued for an adverse experience on ... |
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Anatomy and Physiology
